Secukinumab in adult patients with lichen planus: efficacy and safety results from the randomized placebo-controlled proof-of-concept PRELUDE study.

Background: Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden, representing a population with a clear unmet need for new treatments.
Objectives: To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP) that is inadequately controlled by topical corticosteroids.
Methods: PRELUDE was a randomized double-blind placebo-controlled phase II proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomized to either secukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W) or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator's Global Assessment (IGA) score ≤ 2 at week 16.
Results: Overall, 111 patients were randomized (n = 37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the three cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤ 2 response at week 16 with SECQ4W vs. placebo in the MLP {37.5% [95% credibility interval (Crl) 20.3-57.2] vs. 23.1% (95% Crl 6.5-49.2)} and LPP cohorts [37.5% (95% Crl 20.2-57.3) vs. 30.8% (95% Crl 10.8-57.6)]. In the LPP cohort, a sustained response for IGA ≤ 2 from week 16 to week 32 was achieved with SECQ4W (week 16, 37.5%; week 32, 45.8%), and a substantial improvement was observed in IGA ≤ 2 response in patients from this cohort who switched from placebo (week 16, 30.8%) to SECQ2W after week 16 (week 32, 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals.
Conclusions: PRELUDE is the first randomized controlled basket trial evaluating interleukin (IL)-17A inhibition with secukinumab across three subtypes of LP. Secukinumab was well tolerated and safe, showing different response rates across the three subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of IL-17A across LP subtypes. The novel IGA score showed significant correlation with both patient- and physician-reported outcome measurements.
Competing Interests: Conflicts of interest T.P. has received honoraria and/or consultation fees from AbbVie, Almirall, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, GSK, Incyte, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, UCB Pharma and Vyne Therapeutics. He is a cofounder of YUKIN Therapeutics. B.E. has served as a consultant and/or clinical study investigator for AbbVie, Acelyrin, Aclaris, Allakos, Almirall, Alumis, Amgen, AnaptysBio, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert Pharma, Dermavant Sciences, Dermira Inc., Eli Lilly, Evelo Biosciences, Evommune, Incyte, Janssen, Kymab, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Priovant, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma and Ventyx, and as a paid speaker for Dermavant, Incyte, LEO Pharma, Eli Lilly, Novartis, Ortho Dermatologics, Regeneron and Sanofi Genzyme. J.W. has served as an investigator/advisor and/or speaker for AbbVie, Aclaris, Almirall, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dr Reddy’s, EPI Health, Foamix/Vyne, Galderma, Incyte, Janssen, LEO Pharma, Lilly, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, UCB Pharma and Verrica. M.S. is an investigator, speaker, consultant/advisory board member, and participated in clinical trials with the following companies: AbbVie, Amgen, BMS, Celgene, Galderma, GSK, Janssen Cilag, Leo, Lilly, MSD, Mundipharma, Novartis, Regeneron, Pfizer, Sanofi, and UCB. P.R. has been an investigator, speaker, or member of an advisory board for Bristol Myers Squibb, Concert Pharmaceutical, Ducray, Legacy Healthcare, LEO Pharma, Lilly, L’Oreal Research, Novartis, Pfizer, Pierre Fabre Dermatologie and Vichy Laboratories. J.W. has received grants for scientific projects, clinical studies, lectures or consultancy from the following companies in the last 5 years: Abbott, AbbVie, Actelion, Allergika, Almirall, Aristo, BayPharma, Beiersdorf, Biogen, BMS, Boehringer Ingelheim, Celltrion, Dermapharm, Evolva, Galderma, GSK, Helm, Hexal, Incyte, Infectopharm, Janssen-Cilag, Jenapharm, Johnson & Johnson, Klinge, LEO, Lilly, L’Oréal, Medac, Medice, Mibe, MSD, Mylan, Novaliq, Novartis, Pierre Fabre, Pfizer, Regeneron, Rigi, Skinomics and Wolff. M.H. has received honoraria and/or consultation fees from AbbVie, Argenx, Biotest, Janssen, Novartis, Pfizer, Sanofi Genzyme and Topas Therapeutics. M.R., E.M., H.F., and I.H. are employees and stockholders of Novartis. N.C. was an employee of Novartis Pharma AG at the time of the study and is a stockholder of Novartis.
(© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)